Abstract
Although inborn errors of metabolism do not represent the most common cause of seizures, their early identification is of utmost importance, since many will require therapeutic measures beyond that of common anti-epileptic drugs, either in order to control seizures, or to decrease the risk of neurodegeneration. We translate the currently-known literature on metabolic etiologies of epilepsy (268 inborn errors of metabolism belonging to 21 categories, with 74 treatable errors), into a 2-tiered diagnostic algorithm, with the first-tier comprising accessible, affordable, and less invasive screening tests in urine and blood, with the potential to identify the majority of treatable conditions, while the second-tier tests are ordered based on individual clinical signs and symptoms. This resource aims to support the pediatrician, neurologist, biochemical, and clinical geneticists in early identification of treatable inborn errors of metabolism in a child with seizures, allowing for timely initiation of targeted therapy with the potential to improve outcomes.
Highlights
The occurrence of epilepsy in the general population is relatively common
It is important to consider the possibility of an inborn errors of metabolism (IEMs) in a patient presenting with seizures of an unknown cause due to the amenability to causal treatment of the seizures and the possible co-morbidities, and in order to adequately perform genetic counseling and to more accurately predict the Frontiers in Neurology | www.frontiersin.org van Karnebeek et al Metabolic Evaluation of Epilepsy disease trajectory and prognosis
Given the multitude of aforementioned benefits from establishing an early diagnosis of IEMs, we propose a diagnostic approach in patients with epilepsy, with emphasis on early identification of those amenable to treatment
Summary
The occurrence of epilepsy in the general population is relatively common. Just in the United States, it affects 1.2% of the population, with 3 million adults and 470,000 children suffering from it [1]. A timely diagnosis will avoid unnecessary delay and burden to the patient, it might prevent failed attempts to control seizure with standard antiepileptic drugs, often not without side effects, and it has the potential to decrease the number and cost of unnecessary tests. Even when seizures are the major presenting feature of an IEM, such as in pyridoxine-dependent epilepsy (PDE), diagnosis is often difficult due to the broad differential diagnoses varying from environmental to non-metabolic genetic etiologies (e.g., hypoxic-ischemic encephalopathy or genetic channelopathy) [5]. Patients with early-onset epilepsy can be evaluated in several different departments within a given hospital, which necessitates a standardized testing protocol in order to facilitate effective coordination of the various departments, as well as to avoid unnecessary diagnostic delay. Awareness and subsequent prompt diagnosis has increased survivability as well as expanded the phenotype [6]
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